Translation Regulation of Gene Expression in Toxic Dinoflagellates

有毒甲藻基因表达的翻译调控

• 批准号: 1313888
• 负责人: Rosemary Jagus
• 金额: $ 134.15万
• 依托单位: University of Maryland Center for Environmental Sciences
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-01 至 2019-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1313888&HistoricalAwards=false
• 关键词: Translation; Regulation; Gene; Expression; Toxic

A number of dinoflagellate species are known to produce potent neurotoxins. Their blooms are commonly referred to as "red tides". An understanding of the genetic regulatory mechanisms that affect bloom growth and in particular the development of biomarkers to assess bloom growth status are essential for the development of scientifically sound management and mitigation policies. The genetic organization and regulation of these organisms has been shown to be distinct from nonprotist eukaryotes. Dinoflagellates are remarkable for their extremely large genomes that show little transcriptional regulation and with genes present as multiple tandem copies that are polycistronically processed through coupled trans-splicing and polyadenylation. A broad range of investigations has implicated mRNA recruitment as a major site of regulation of gene expression. However, relatively little is understood regarding translational initiation and its regulation in these organisms. In this project, a research team centered at the University of Maryland Institute of Marine and Environmental Technology will attempt to unravel the roles of the likely key players in translational regulation, eIF2 and eIF4, along with the spliced leader cap structures in regulating gene expression. Using the icthyotoxic dinoflagellate, Karlodinium veneficum and the toxin producing Karenia brevis, they will (1) determine whether changes in eIF2á phosphorylation underlie diel changes in gene expression or responses to different stressors; (2) begin characterization of the eIF2á-kinases from K. veneficum; (3) characterize the ability of K.veneficum eIF4E family member to bind to cap structures and translational binding partners; and (4) assess the role of K.veneficum eIF4E members in mRNA recruitment. Given the central role of translation in dinoflagellate gene expression, this should provide significant insight into mechanisms relevant to dinoflagellate growth, toxicity, and the regulation of harmful algal blooms. These results are expected to define a new paradigm for translational regulation in dinoflagellates, thus offering an innovative approach to bridge the gap between genomics and physiological complexity in dinoflagellates. Understanding the mechanism of translational regulation of dinoflagellate gene expression may begin to provide insight into the regulation of toxin production by these organisms and may be of direct use in monitoring/managing harmful algal blooms. Broader Impacts: The studies will provide critical insight into mechanisms relevant to dinoflagellate growth, toxicity, and the regulation of harmful algal blooms, with a long term goal of providing avenues for intervention. The project will provide research experiences/training to high school students, undergraduate interns and area high school teachers. JOINT FUNDING BY NSF AND NIEHS: The original proposal on which this project is based (R01 ES021949-01) was submitted to the National Institutes of Environmental Health Sciences (NIH/NIEHS) in response to Funding Opportunity Announcement RFA-ES-11-013 , "Oceans, Great Lakes and Human Health (R01)", an opportunity jointly sponsored by NSF. This project is cooperatively funded through separate awards from NSF and NIEHS.

已知许多甲藻物种会产生强效神经毒素。它们的绽放通常被称为“赤潮”。了解影响水华生长的遗传调控机制，特别是开发评估水华生长状态的生物标志物，对于制定科学合理的管理和缓解政策至关重要。这些生物体的遗传组织和调控已被证明与非原生真核生物不同。甲藻因其极其庞大的基因组而引人注目，这些基因组几乎没有转录调控，并且基因以多个串联拷贝的形式存在，这些拷贝通过耦合的反式剪接和多腺苷酸化进行多顺反子加工。广泛的研究表明 mRNA 募集是基因表达调控的主要位点。然而，人们对这些生物体中的翻译起始及其调节知之甚少。在该项目中，以马里兰大学海洋与环境技术研究所为中心的研究小组将尝试阐明翻译调控中可能的关键参与者 eIF2 和 eIF4 的作用，以及剪接的前导帽结构在调节基因表达中的作用。利用鱼毒甲藻、Karlodinium v​​eneficum 和产生毒素的 Karenia brevis，他们将 (1) 确定 eIF2á 磷酸化的变化是否是基因表达或对不同应激源反应的昼夜变化的基础； (2) 开始表征 K. veneficum 的 eIF2á-激酶； (3)表征K.veneficum eIF4E家族成员结合帽结构和翻译结合配偶体的能力； (4) 评估 K.veneficum eIF4E 成员在 mRNA 招募中的作用。鉴于翻译在甲藻基因表达中的核心作用，这应该为与甲藻生长、毒性和有害藻华调节相关的机制提供重要的见解。这些结果有望定义甲藻翻译调控的新范式，从而提供一种创新方法来弥合甲藻基因组学和生理复杂性之间的差距。了解甲藻基因表达的翻译调节机制可能会开始深入了解这些生物体产生毒素的调节，并可能直接用于监测/管理有害藻华。更广泛的影响：这些研究将为与甲藻生长、毒性和有害藻华调节相关的机制提供重要见解，长期目标是提供干预途径。 该项目将为高中生、本科生实习生和地区高中教师提供研究经验/培训。 NSF 和 NIEHS 联合资助：该项目所依据的原始提案 (R01 ES021949-01) 已提交给美国国立环境健康科学研究所 (NIH/NIEHS)，以响应资助机会公告 RFA-ES-11-013“海洋、五大湖和人类健康 (R01)”，该机会由 NSF 联合赞助。 该项目由 NSF 和 NIEHS 分别资助。